First, we analyzed the binding characteristics of insulin glargine and its metabolites M1, M2, and IM to IR-A and IR-B. Using plasma membranes from CHO cells that overexpress the receptor isoforms, the IC
50
value for competition of unlabeled ligand with a constant concentration of radioactively labeled human insulin were determined as a measure of affinity. The results are shown in
Table 1
with representative competition curves given in
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. Both IR isoforms bound human insulin with high affinity that did not significantly (p = 0.23) differ between IR-A (IC
50
= 0.49 nmol/L) and IR-B (IC
50
= 0.57 nmol/L). In contrast, IR-A displayed a considerably higher affinity for IGF-1 (2.7-fold) and IGF-2 (7.5-fold) than IR-B, but the affinity of IR-A and IR-B for IGF-1 were approximately 130- and 300-fold, respectively, less potent than those for human insulin. Both isoforms bound IGF-2 with higher affinity than IGF-1 but with lower affinity than human insulin. These data are consistent with results published previously
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–
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and demonstrated the validity of our experimental system.

Figure 2.
Binding and signaling of insulin glargine and its metabolites to the human insulin receptor isoform A and B.

Binding of the insulin analogs to the human IR-A (
A
) or IR-B (
B
) was analyzed in a competitive binding assay using SPA technology. The binding of a constant concentration of [
125
I]insulin to plasma membranes from CHO cells overexpressing either IR-A or IR-B was measured in presence of increasing concentrations of unlabeled competing ligand after incubation at room temperature for 12 h. All data has been corrected for non-specific binding and are expressed as percentage of [
125
I]insulin in absence of competing ligand. To analyze the insulin-stimulated activation and subsequent autophosphorylation of the insulin receptor CHO cells overexpressing the human IR-A (
C
) or IR-B (
D
) were stimulated for 15 min at 37°C with increasing concentrations of peptides, then the cells were fixed with 3.7% PFA and the amount of phosphotyrosines was analyzed via In-Cell Western. The data represent mean values ± SEM of at least 3 individual experiments measured in quadruplicate.

Insulin glargine and its metabolites IM, M1, and M2 showed no difference in their respective binding affinities to the two IR isoforms and were only 40–50% less active than human insulin. In contrast, [Asp
B10
]insulin showed significant isoform selectivity, being 3.5-fold more active towards IR-A (p<0.01), and was 8.2- and 2.7-fold more potent in binding to IR-A and IR-B, respectively, relative to human insulin.

Post-trial motions are employed after the jury (or judge, in a bench trial) renders its verdict. These motions are to be differentiated from those made at the close of evidence, which was covered in the earlier chapter on trial practice.

The first motion to consider is a motion for a new trial. See Federal Rule of Civil Procedure (“FRCP”) 59. A party may move the court for a new trial in particular situations, and it is up to the trial court’s discretion whether to grant the motion. The rules provide for an order granting a new trial, or similar relief, to remedy a situation where the judgment rendered in the case is a miscarriage of justice. There are many grounds on which a party may base its motion for a new trial; these grounds are not codified, but have been established by the common law. Following are the various grounds on which a party may rely in seeking a new trial:

1) The case where the Verdict is Against the Weight of the Evidence:
A motion for a new trial can be sustained where evidence and testimony presented strongly supports one party, but the judgment is for the other. One court has explained that the power to grant a motion for a new trial

2) The case where the Verdict is Inadequate or Excessive:
This is the case where the jury’s award is either grossly inadequate or grossly excessive. Some courts have referred to such verdicts as ‘shocking’ to the court’s conscience. For example:

3) The case where a Party Newly Discovers Evidence:

Similarly, a
change in law
after the final judgment is not a sufficient basis on which to move for a new trial. See
Title v. United States
, 263 F.2d 28 (9th Cir. 1959).

Other grounds for a new trial include
improper conduct by the court or by counsel and improper conduct affecting the jury
. As you might imagine, this may occur when the jury is influenced improperly.

FRCP Rule 59 is clear that following a bench trial,

In other words, following a bench trial, the court has broad discretion to re-open the case and amend the judgment if new facts come to light.

The motion for a new trial must be filed no later than ten days after the judgment is entered. FRCP 59(b). While the motion must specify the grounds upon which the party is relying, after giving the parties notice and an opportunity to be heard, the court may order a new trial on a ground not specified in the motion for a new trial.

It is not only upon a party’s motion that the court may order a new trial. Under FRCP 59(d), the court may,
sua sponte
, that is, on its own, order a new trial on any ground on which a party could base its motion. If the court orders a new trial
sua sponte
or grants a motion for a reason not specified in the moving papers, the court must specify the applicable ground(s) upon which it is relying in its order. The court, however, is subject to the same time limitations are imposed on a party's motion for a new trial.

Components enable designers to create reusable Instances of UI elements, manage state and can keep your designs more consistent and manageable. When the master component is updated, the instances update automatically.

Component Instances

Component instances can be nested inside master components. This allows for small, detailed components to be combined with others into larger, more complex interfaces while maintaining granular control over each individual component that syncs between instances.

Inheritance is defined on a per-property basis so designers don’t need to create individual components for each state.

Properties that affect the layout of child layers
are
not
overridable on instances, allowing you to maintain a stricter level of consistency with less effort.

Examples of these properties include:

In addition, you cannot add, remove, or reorder layers within instances of components.

Other properties
are
able to be overridden and allow designers to create variations on the original component to represent state and data while maintaining overall consistency within an interface.

Select any layer, group, or frame and click the component icon in the toolbar, or use the
Option + Command + K
shortcut to convert your selection into a component.

It's not possible to duplicate a component in a single file. When you duplicate a component in a file it will always create an instance of the original component.

However, when you copy a component from file A and paste it into file B, you will have a fully functioning component in file B.

There are a few way to create an instance of a component. First, select the original component and then:

When selecting an instance, right-click and select
Go to Master Component
. The viewport will snap to the original component’s location and the component will be selected.

When the instance is selected, there's also a shortcut just under the Instances section in the
Properties Panel
.

The
Reset Instance
icon appears in the toolbar when:

In the example above, the original component (Play Button - Master) is red. Two instances were made and fill overrides were made; one green and one blue.

When either instance is selected the option to
Reset Instance
appears. This allows you to revert selected instances to its original properties and reconnect its inheritance to the original component. After you
Reset Instance
, changes made to the master component will again be propagated to the instances.

This also works for any selected layer in the instance.

In the example above, we have the text layer of the blue instance selected. We have overridden the original PLAY text in this instance with
bold
and
italic
. With the text layer selected we can
Reset Instance
.